Polyalkoxy fatty compound

ABSTRACT

Provided is a polyalkoxy fatty compound having the structure (I) 
     
       
         
         
             
             
         
       
         
         
           
             wherein R 1  is a fatty group; R 2  is H or a substituted or unsubstituted hydrocarbyl group; n is 0 to 5; X 1  is S, or NH; X 2  is O, S, or NH; and R 3  is a polymeric group comprising polymerized units of structure (II) and structure (III)

It is often desired to provide an aqueous solution of a protein. It isdesired that such aqueous solutions remain stable for a long time. Lackof stability includes, for example, either or both of the followingprocesses: denaturing of the protein or agglomeration of the proteinmolecules.

U.S. Pat. No. 5,635,461 describes an anionic surfactant having theformula

It is desired to provide a surfactant that provides improved stabilityto an aqueous solution of protein. It is also desired to provide amixture of such a surfactant with a protein, where the mixture can forman aqueous solution of the protein, where the solution has goodstability.

The following is a statement of the invention.

A first aspect of the present invention is a polyalkoxy fatty compoundhaving the structure (I)

wherein R¹ is a fatty group; R² is H or a substituted or unsubstitutedhydrocarbyl group; n is 0 to 5; X¹ is S or NH; X² is O, S, or NH; and R³is a polymeric group comprising polymerized units of structure (II) andstructure (III)

If n is 2 or greater, the various X₁ groups may be different from eachother or the same as each other, or any combination thereof. If n is 2or greater, the various R² groups may be different from each other orthe same as each other, or any combination thereof.

A second aspect of the present invention is a composition comprising oneor more protein and one or more polyalkoxy fatty compound, wherein theweight ratio of said protein to said polyalkoxy fatty compound is from0.05:1 to 200:1, and wherein said polyalkoxy fatty compound hasstructure (I)

wherein R¹ is a fatty group; R² is H or a substituted or unsubstitutedhydrocarbyl group; n is 0 to 5; X¹ is O, S, or NH; X² is O, S, or NH;and R³ is a polymeric group comprising polymerized units of (II) and(III)

The following is a detailed description of the invention.

As used herein, the following terms have the designated definitions,unless the context clearly indicates otherwise.

A polyalkoxy compound is a compound that contains one or more grouphaving the structure -(-A-O)_(m)—, where m is three or more, and A is anunsubstituted alkyl group. The group A may be linear, branched, cyclic,or a combination thereof. The various A groups among the various-(-A-O)— groups may be the same as each other or different.

A fatty compound is a compound that contains one or more fatty group. Afatty group is a group that contains 8 or more carbon atoms, each ofwhich is bonded to one or more of the other carbon atoms in the group. Apolyalkoxy fatty compound is a compound that is both a polyalkoxycompound and a fatty compound.

A hydrocarbyl group is a group that contains hydrogen and carbon atoms.An unsubstituted hydrocarbyl group contains only hydrogen and carbonatoms. A substituted hydrocarbyl group contains one or more substituentgroup that contains one or more atom other than hydrogen and carbon.

A polymeric group is a relatively large group made up of the reactionproducts of smaller chemical repeat units. Polymeric groups havenumber-average molecular weight of 500 or more. Polymeric groups mayhave structures that are linear, branched, star shaped, looped,hyperbranched, crosslinked, or a combination thereof; polymeric groupsmay have a single type of repeat unit (“homopolymeric groups”) or theymay have more than one type of repeat unit (“copolymeric groups”).Copolymeric groups may have the various types of repeat units arrangedrandomly, in sequence, in blocks, in other arrangements, or in anymixture or combination thereof.

Molecules that can react with each other to form the repeat units of apolymeric group are known herein as “monomers.” The repeat units soformed are known herein as “polymerized units” of the monomer. Acompound containing one or more polymeric group is a polymer.

A protein is a polymer in which the polymerized units are polymerizedunits of amino acids. The amino acids are bonded together by peptidebonds. A protein contains 20 or more polymerized units of one or moreamino acids. The term protein includes linear polypeptide chains as wellas more complex structures that contain polypeptide chains.

A protein is considered to be in solution in a liquid medium (or,synonymously, dissolved in the liquid medium) if the molecules of theprotein are distributed throughout the continuous liquid medium in theform of dissolved individual molecules. The protein is considered to bedissolved in water if the continuous liquid medium contains water in theamount of 60% or more by weight based on the weight of the continuousliquid medium.

A chemical group is an ionic group if there is a pH value between 4.5and 8.5 such that, when the chemical group is in contact with water atthat pH value, 50 mole % or more of those chemical groups present are inionic form.

A buffer is either (i) a compound that has the ability to accept aproton to form the conjugate acid of that compound, and the conjugateacid of that compound has pKa of less than 9, or (ii) a compound thathas the ability to release a proton, and the compound has pKa of greaterthan 5.

When a ratio is said herein to be X:1 or greater, it is meant that theratio is Y:1, where Y is greater than or equal to X. For example, if aratio is said to be 3:1 or greater, that ratio may be 3:1 or 5:1 or100:1 but may not be 2:1. Similarly, when a ratio is said herein to beW:1 or less, it is meant that the ratio is Z:1, where Z is less than orequal to W. For example, if a ratio is said to be 15:1 or less, thatratio may be 15:1 or 10:1 or 0.1:1 but may not be 20:1.

The composition of the present invention is a polyalkoxy fatty compoundhaving the structure (I)

where R¹ is a fatty group; R² is H or a substituted or unsubstitutedhydrocarbyl group; n is 0 to 5; X¹ is O, S, or NH; X² is O, S, or NH;and R³ is a polymeric group comprising polymerized units of structure(II) and structure (III)

Preferably R¹ is a substituted or unsubstituted aliphatic group. Amongsubstituted aliphatic groups, preferred substituent is hydroxyl. Morepreferably R¹ is an unsubstituted aliphatic group; more preferably, R¹is an unsubstituted alkyl group. Preferably, R¹ is linear. Preferably,R¹ has 9 or more carbon atoms; more preferably 10 or more. Preferably,R¹ has 22 or fewer carbon atoms; more preferably 20 or fewer; morepreferably 18 or fewer; more preferably 16 or fewer.

Preferably, X¹ is NH. Preferably, X² is O or NH; more preferably NH.

Preferably, R² has 20 or fewer atoms; more preferably 15 or fewer.Preferably, if R² is not hydrogen, then R² contains one or more carbonatom. Preferably, R² is either hydrogen or an unsubstituted hydrocarbongroup; more preferably, R² is either hydrogen, an unsubstituted alkylgroup, or an alkyl group whose only substituent is an unsubstitutedaromatic hydrocarbon group. Among unsubstituted alkyl groups, preferredis methyl. Among alkyl groups whose only substituent is an unsubstitutedaromatic hydrocarbon group, preferred is —CH₂—(C₆H₅), where —(C₆H₅) is abenzene ring. Preferably, R² is chosen so that a compound with thestructure (IV)

would be one of the 20 canonical biological amino acids.

Preferably, R³ has number-average molecular weight of 600 or higher;more preferably 800 or higher. Preferably, R³ has number-averagemolecular weight of 10,000 or less; more preferably 5,000 or less; morepreferably 3,000 or less; more preferably 2,500 or less; more preferably2,000 or less; more preferably 1,500 or less. Preferably, the group R³is either a statistical copolymer of (II) and (III) or a block copolymerof (II) and (III); more preferably the group R³ is a statisticalcopolymer of (II) and (III). Preferably, —R³ has the structure —R⁴—CH₃,where R⁴ is a polymeric group comprising polymerized units of structure(II) and structure (III). Preferably, R⁴ has no other polymerized unitsin addition to structure (II) and (III).

Preferably, n is 0 or 1.

It is useful to characterize the mole ratio (herein the “PO/EO ratio”)of units of structure (II) to units of structure (III). Preferably, thePO/EO ratio is 0.01:1 or greater; more preferably 0.02:1 or greater;more preferably 0.05:1 or greater; more preferably 0.1:1 or greater.Preferably, the PO/EO ratio is 2:1 or less; more preferably 1.5:1 orless; more preferably 1:1 or less; more preferably 0.5:1 or less.

Preferably, the compound of structure (I) has no ionic groups.

The compound of structure (I) may be made by any method. A preferredmethod is to react a compound having structure NH₂—R³ with a compoundselected from compounds of structure V

and compounds of structure VI

where X³ is O, S, or NH. Preferences for R¹, X², R², R³, and n are thesame as those described above. Preferably, X³ is O.

A more preferred method of making some embodiments of the compound ofstructure (I) is as follows. In a first step, an acyl chloride isreacted with an amino acid to form a carboxyl-functional fatty amide asfollows:

Then, in a second step, the carboxyl-functional fatty amide is reactedwith an amine-terminated polyalkoxy compound, as follows:

where PO is structure (II) and EO is structure (III).

A preferred use of the compound of structure (I) is in a compositionthat contains one or more protein and one or more compound of structure(I).

Preferred proteins have 40 or more polymerized units of amino acids;more preferably 100 or more.

Preferred proteins are selected from monoclonal antibodies, growthfactors, insulins, immunoglobulins, polyclonal antibodies, hormones,enzymes, polypeptides, fusions of peptides, glycosylated proteins,antigens, antigen subunits, or combinations thereof. Preferred proteinshave therapeutic efficacy to treat a disease or medical condition or tofunction as vaccines. Also contemplated are proteins that have abeneficial effect on a food composition or a cleaning composition or acoatings formulation.

Preferably, the weight ratio of protein to compound of structure (I) is0.1:1 or greater; more preferably 0.2:1 or greater; more preferably0.5:1 or greater; more preferably 0.9:1 or greater. Preferably, theweight ratio of protein to compound of structure (I) is 150:1 or less;more preferably 100:1 or less.

A preferred method of making a formulation that contains both a proteinand a compound of structure (I) is to mix together water, one or moreprotein, one or more compound of structure (I), and optional additionalingredients to make a formulation (herein called formulation “F1”) inwhich protein is dissolved in water.

Preferably, the amount of water in formulation F1, by weight based onthe weight of formulation F1, is 50% or more; more preferably 60% ormore; more preferably 70% or more.

In formulation F1, preferably the molecules of protein are notaggregated into large particles, even if the aggregated particles aredispersed in the liquid medium. Preferably, if any aggregated particlesthat contain protein molecules are present, the volume-average diameterof such particles is 10 nm or smaller; more preferably 6 nm or smaller.

In formulation F1, preferably the amount of protein is 0.01 mg/mL ormore; more preferably 0.1 mg/mL or more; more preferably 0.9 mg/mL ormore; In formulation F1, preferably the amount of protein is 400 mg/mLor less; more preferably 300 mg/mL or less; more preferably 250 mg/mL orless.

In formulation F1, preferably the amount of compound of structure (I) is0.01 mg/mL or more; more preferably 0.1 mg/mL or more; more preferably0.5 mg/mL or more. In formulation F1, preferably the amount of compoundof structure (I) is 50 mg/mL or less; more preferably 10 mg/mL or less;more preferably 5 mg/mL or less.

Formulation F1 optionally contains one or more additional ingredients.Additional ingredients are compounds other than water, proteins, andcompounds having structure (I). Preferred additional ingredients aresurfactants not having structure (I), sugars, salts, buffers, aminoacids, salts of amino acids, and mixtures thereof. When such additionalingredients are present, preferably the total amount of all additionalingredients is 300 mg/mL or less.

For inclusion in formulation F1, among surfactants not having structure(I), preferred are nonionic surfactants; more preferred arepolyoxyethylene derivatives of sorbitan monolaurate (for example,polysorbate 20 and polysorbate 80) and triblock copolymers having acentral block of polymerized units of propylene oxide and end blocks ofpolymerized units of ethylene oxide (for example polyoxamer F127 andpolyoxamer 188).

For inclusion in formulation F1, preferred sugars are sucrose, glucose,mannose, trehalose, maltose, and mixtures thereof.

For inclusion in formulation F1, preferred salts have cations chosenfrom hydrogen, sodium, potassium, magnesium, calcium, ammonium, andmixtures thereof. Preferred salts have anions chosen from fluoride,chloride, bromide, iodide, phosphate, carbonate, acetate, citrate,sulfate, and mixtures thereof. Preferred buffers have cations chosenfrom hydrogen, sodium, potassium, magnesium, calcium, ammonium, andmixtures thereof. Preferred buffers have anions chosen from fluoride,chloride, bromide, iodide, phosphate, carbonate, acetate, citrate,sulfate, and mixtures thereof.

For inclusion in formulation F1, preferred amino acids and salts thereofare selected from lysine, glycine, arginine, histidine, and mixturesthereof.

In formulation F1, it is contemplated that the particles that containprotein are dissolved in a continuous aqueous medium. Of the compoundsother than proteins that are present in formulation F1, each compoundmay, independently of the other compounds, be found dissolved in theaqueous medium; found in dispersed particles that do not containprotein; found attached to some or all of the dissolved molecules ofprotein; or found distributed between two or more of these locations.

It is contemplated that formulation F1 will have good stability. Thatis, it is contemplated that formulation F1 will resist denaturing of theprotein and will resist agglomeration of the dissolved molecules intoagglomerated particles.

One method of storing and/or transporting the mixture of protein andcompound of structure (I) is to make a formulation F1 and then removethe water from formulation F1 through a drying process. It iscontemplated that the solid material produced by drying formulation F1(herein called solid “S1)” can be easily stored and transported withoutdenaturing the protein or other degradation. It is further contemplatedthat, after transportation and/or storage, solid S1 can be mixed withwater to produce a solution that has properties similar to theproperties of formulation F1.

The following are examples of the present invention.

Procedures were conducted at room temperature, approximately 23° C.,except where otherwise stated.

The following terms and abbreviations are used.

-   BSA=bovine serum albumin-   IgG=immunoglobulin G; typically available from rabbit or human    serum; in the examples below, the source of the IgG is noted.-   THF=tetrahydrofuran-   PO=structure (II)-   EO=structure (III)-   PEA1=Jeffamine™ M1000 polyetheramine (Hunstman), approximate    molecular weight of 1,000, and PO/EO ratio of 3/19-   PEA2=Jeffamine™ M2070 polyetheramine (Hunstman), approximate    molecular weight of 2070, and PO/EO ratio of 10/31

Dynamic Light Scattering (DLS) measurements were performed as follows.Light scattering measurements were performed on a Wyatt DyanaPro™ highthroughput DLS instrument. Samples were prepared with variable proteinconcentration and 1 mg/mL surfactant in citrate-saline buffer, pH 7, 15millimolar sodium citrate, 150 millimolar sodium cloride. Orencia™ andRemicade™ powders were reconstituted with water rather than buffer. 30μL of each sample were placed in the wells of an Aurora 384 well blackcycloolefin polymer plate with clear bottom (Brooks Life ScienceSystems). On top of each well, 15 μL of silicone oil were added. Fortemperature ramp studies, the samples were allowed to equilibrate at 25°C. and then were ramped to 80° C. at 0.05 C/min. DLS measurements wereobtained continuously, cycling from well to well with 5×3 secacquisitions per well per cycle. For isothermal studies, the sampleswere ramped at 1° C./min to 40° C., 50° C., and the final temperature(50° C. for Remicade, 65° C. for BSA, 73° C. for Orencia) and data werecollected continuously over approximately 36 hours.

The circular dichroism experiments (CD) were conducted on a JASCO J-1500CD spectropolarimeter. Protein solutions [5% BSA (50 mg/mL), and 0.2%IgG (2 mg/mL)] were prepared in 10 mM phosphate buffered saline (PBS)buffer pH, 7.3. BSA samples were diluted 1:10 with PBS buffer beforemeasurement.

Nano-Differential Scanning Calorimetry (nano-DSC) was performed using aModel 6100 Nano II DSC, Calorimetry Science Corporation, USA. Both thesample (typically 2.5 mg/ml protein solution) and the reference(phosphate buffer) were scanned at a pressure of 0.3 MPa (3 bars) and at1° C./min scan rate. Scanning was from 15° C. to 105° C.

Synthesis of compound of structure (I) (“surfactant”) was performed asfollows:

N-myristoyl amino acid derivative was prepared by the reaction ofmyristoyl chloride with glycine in the presence of sodium hydroxide andtriethylamine at room temperature (approximately 23° C.) for 4 hours.The N-myristoyl amino acid derivative (5 mmol) and polyetheramine(either PEA1 or PEA2) (5 mmol amine group) were added to a 50 mLone-neck round bottom flask containing a stir bar and fitted with acondenser and gas inlet adapter. The flask was placed into an oil bathand was heated as follows: 1 h at 100° C., 1 h at 125° C., 1 h at 150°C., 1.5 h at 175° C., and 1.5 h at 200° C. During this time, waterevolution was observed once the reaction temperature reached 175-200° C.The reaction mixture was cooled to room temperature (approximately 23°C.), vacuum was applied to the flask, then the flask was reheated for 30min at 100° C., 30 min at 125° C., 30 min at 150° C., 30 min at 175° C.,and 2 h at 200° C. Heating was discontinued and the reaction mixture wasallowed to cool to room temperature and then the flask was back-filledwith nitrogen. 1H and 13C NMR spectra were consistent with thestructures of the surfactants.

For compounds of structure (I) with n=0, the myristoyl chloride wasreacted directly with the Jeffamine resin as described above.

In each inventive surfactant that was made, R¹— was CH₃(CH₂)₁₁CH₂—. X¹and X² were both N. R³ was a copolymer of proplyene oxide units andethylene oxide units, end capped with a methyl group.

The inventive surfactants that were made were as follows:

Example Label n R² PEA 1 GM1000 1 H PEA1 2 AM1000 1 CH₃ PEA1 3 FM1000 1note⁽¹⁾ PEA1 4 0M1000 0 none PEA1 5 GM2000 1 H PEA2 note⁽¹⁾:

EXAMPLE 1: TESTING OF PROTEIN SOLUTIONS CONTAINING BSA

Scanning DLS of 5 mg/mL BSA with various surfactants as indicated. Scanspeed was 0.05° C./min from 25 to 80° C. Surfactants were all 1 mg/mL.In scanning DLS, samples were tested for volume-average particlediameter as a function of temperature. Each sample eventually showed anincrease in diameter. The temperature of the onset (T_(onset)) wasrecorded. Higher T_(onset) means a more stable protein solution.

Nano-DSC of BSA (5 mg/mL) was performed with various surfactants (5mg/mL). The Nano-DSC graph of heat flow vs. temperature shows a peakbetween 60° C. and 85° C. that is labeled the “unfolding” peak, and itindicates the temperature at which the protein denatures at maximalrate. The temperature of the unfolding peak (Tm) is reported. Higher Tmmeans a more stable the protein solution.

Circular dichroism (CD) BSA samples (5 mg/mL) with different surfactantswere measured following heat aging at 70° C. for 30 minutes. The graphof CD vs. wavelength shows a peak at 222 nm, indicating absorbance ofthe alpha-helix. Decrease in the alpha-helix peak indicatesdenaturation. For each sample, the CD at 222 nm was examined, and thedifference between the value of the initial sample was compared to thevalue of the same sample after heat aging at 70° C. for 30 minutes; thisdifference is reported as ΔCD. Higher absolute value of ΔCD means a lessstable protein solution.

Also performed was isothermal DLS of BSA (5 mg/mL) with 1 mg/mLsurfactants at 62° C. Volume-average particle diameter was measured as afunction of time. The diameter at 2000 seconds (D2k) was recorded. Lowervalue of D2k means a more stable protein solution.

Results were as follows. “nt” means not tested.

T_(onset) Tm Type Surfactant (° C.) (° C.) ΔCD (mdeg) D2k (nm)comparative none 57 61 −30 >100 comparative polysorbate 20 62 74 −24 11comparative polysorbate 80 60 74 nt 12 comparative n-dodecyl 62 nt nt 10b-maltoside inventive Example 3 70 76 3.9⁽²⁾ nt inventive Example 5 59nt −18.7 nt inventive Example 2 72 68 −9.9 nt inventive Example 4 75 840.5⁽²⁾ 6.5 inventive Example 1 64 73 −10.8 nt note ⁽²⁾values of 4 orless are considered to be equivalent to zero in view of experimentalvariability.

In the T_(onset) results, all the inventive examples showed comparableor superior stability to the comparative examples, and Examples 2, 3,and 4 were especially superior to the comparative examples. In the Tmresults, all the inventive examples showed comparable or superiorstability to the comparative examples, and Example 4 was especiallysuperior to the comparative examples. In the ΔCD results, all theinventive examples showed results far superior to the comparativesamples. In the D2k results, the only inventive example tested, Example4, was superior to the comparative examples.

EXAMPLE 2: TESTING OF PROTEIN SOLUTIONS CONTAINING IGG

Scanning DLS was performed on protein solutions containing 1 mg/mL IgGfrom rabbit, at 0.05° C./min from 25° C. to 80° C., with surfactants all1 mg/mL. T_(onset) was 66° C. for all samples, but, as temperature wasincreased above T_(onset), the sample using Example 1 showed much slowergrowth of particle diameter than all the other samples.

Isothermal DLS was performed at 1 mg/mL rabbit IgG at 65° C., and sizeat 4000 seconds (D4k) was reported. CD technique using human IgGcompared change in absorbance at 218 nm due to heat aging at 65° C. for18 hours. Results were as follows:

Type Surfactant D4k (nm) ΔCD (mdeg) comparative none >200 −22comparative polysorbate 20 22 −21 comparative polysorbate 80 30 ntcomparative alkyl maltoside 30 nt inventive Example 3 12.2 −15.5inventive Example 5 40 nt inventive Example 2 30 −16 inventive Example 425 −18 inventive Example 1 25 −17.5

In the ΔCD results, the inventive examples were superior to thecomparative examples. In the D4k results, Example 3 was superior to thecomparative examples.

EXAMPLE 3: RESULTS USING ORENCIA™ POWDER

ORENCIA™ (abatacept) powder (manufactured by Bristol-Myers Squib) wasobtained by prescription. Orencia was diluted with water to 4 mg/mL andtested by scanning DLS for T_(onset). Also, Orencia was diluted to 10mg/mL with water and tested by isothermal DLS at 73° C., and thediameter was noted at 20 hours (D20h). In protein solutions, D20h tendsto grow larger as time passes, and less-stable solutions reach highervalues of D20h. Smaller value of D20h means a more stable proteinsolution. Orencia solutions at 1 mg/mL were tested in an isothermal stepexperiment; particle diameter was measured by DLS as a function of timeduring a hold of 45 hours at 50° C., followed by 15 hours at 60° C. Thediameter at the end of this process, Dstep, was recorded. Smaller valuesof Dstep means a more stable protein solution.

Results were as follows.

Type Surfactant T_(onset) (° C.) D20h (nm) Dstep (nm) comparative none62 >100 >100 comparative polysorbate 20 62 6 5 comparative polysorbate80 53 7 5.5 comparative poloxamer 188 70 6 5.1 comparative alkylmaltoside 69 4.9 4.1 inventive Example 3 >80 5.6 4.7 inventive Example 572 5.7 5.1 inventive Example 4 75 5.4 4.9

In the T_(onset) and D20h results, the inventive samples had more stableprotein solutions than the comparative samples.

EXAMPLE 4: TEST RESULTS ON REMICADE™

REMICADE™ (infliximab) powder (manufactured by Johnson and Johnson) wasobtained by prescription. Remicade powder was diluted to 1 mg/mL inwater. Using scanning DLS, T_(onset) was measured as described above.Also, isothermal DLS was performed at 50° C., and the time at which theparticle diameter began to grow rapidly (t-grow) was noted. Results wereas follows:

Type Surfactant T_(onset) (° C.) t-grow (min) comparative none 54 <10comparative polysorbate 20 53 1400 comparative polysorbate 80 54 1400comparative alkyl maltoside 53 625 inventive Example 3 53 535 inventiveExample 5 53 1100 inventive Example 2 53 250 inventive Example 4 53 175inventive Example 1 53 870The inventive samples showed comparable performance to the comparativesamples.

1. A polyalkoxy fatty compound having the structure (I)

wherein R¹ is a fatty group; R² is H or a substituted or unsubstitutedhydrocarbyl group; n is 0 to 5; X¹ is S or NH; X² is O, S, or NH; and R³is a polymeric group comprising polymerized units of structure (II) andstructure (III)


2. The polyalkoxy fatty compound of claim 1, wherein —R³ has thestructure —R⁴—CH₃, wherein R⁴ is a polymeric group comprisingpolymerized units of (II) and (III)


3. The polyalkoxy fatty compound of claim 1, wherein —R³ has no ionicgroups.
 4. The polyalkoxy fatty compound of claim 1, wherein —R³ hasnumber-average molecular weight from 600 to 10,000.
 5. The polyalkoxyfatty compound of claim 1, wherein —R² has 20 or fewer atoms.
 6. Thepolyalkoxy fatty compound of claim 1, wherein —R¹ is a linearunsubstituted alkyl group.
 7. The polyalkoxy fatty compound of claim 1,wherein —R¹ is a linear unsubstituted alkyl group having 10 to 16 carbonatoms, wherein —R² is selected from the group consisting of hydrogen,methyl, and —CH₂—(C₆H₅), wherein —(C₆H₅) is a benzene ring, and wherein—R³ has number-average molecular weight from 800 to
 3000. 8. A method ofmaking the polyalkoxy fatty compound of claim 1, wherein said methodcomprises reacting a compound having structure NH₂—R³ with a compoundselected from compounds of structure V

and compounds of structure VI

wherein X³ is S, or NH.